Death Strikes Young in RA

Most common causes were circulatory, respiratory, and malignancy

Action Points

Note that this large, population-based cohort study found that individuals with rheumatoid arthritis died of similar causes as the general population, but earlier.

Among younger patients, a substantially increased risk of death from pulmonary causes was noted, suggesting a pathogenic role for the lung involvement that often accompanies rheumatoid arthritis.

The causes of death among patients with rheumatoid arthritis (RA) in Ontario were similar to what was seen in the general population, but the deaths occurred at younger ages, a Canadian study found.

The most common reported causes of death for both RA patients and comparison individuals were diseases of the circulatory system (29% and 30%), cancer (26% and 33%), and respiratory diseases including infections (12% and 9%), according to Jessica Widdifield, PhD, of McGill University in Montreal, and colleagues.

Overall, 36% of patients with RA died prematurely, which was defined as before age 75, compared with 32% of the general population, the researchers reported in Arthritis Care & Research.

"In Canada, all-cause mortality rates for RA patients remain elevated compared with the general population, with 40% to 50% greater mortality risk among RA patients. Knowledge about the cause of death in RA is important for understanding the natural history of the disease and focusing prevention efforts."

The team therefore undertook a population-based study of health administrative databases in Ontario, with its 13.5 million residents and single-payer healthcare system, identifying all RA cases diagnosed from 2000 to 2013. Four matched controls were selected for each case, for a total of 87,114 RA patients and 348,456 comparators.

Mean age was 56.7, and 70% were women. At the time of entry into the cohort, RA patients more often had co-morbidities, including hypertension, chronic obstructive pulmonary disease (COPD) or asthma, and coronary artery disease. Among those who died, the burden of co-morbid disease before death also was high, with a greater frequency of COPD or asthma, acute renal failure, and coronary artery disease.

Participants were followed for an average of 5 years, with some followed for up to 13 years. During follow-up, 14% of the RA patients and 9% of comparators died, resulting in mortality rates of 232 and 184 per 10,000 patient-years.

The overall excess mortality rate from all causes was 48.2 excess deaths per 10,000 patient-years. For circulatory diseases, the excess mortality rate was 12.8 excess deaths per 10,000, and for respiratory diseases, it was 11.5 excess deaths. There were no excess deaths for cancer.

The researchers also calculated mortality rate ratios (MRRs), detecting greater risks for overall and cause-specific mortality. Highest risks for the latter were diseases of the following:

Musculoskeletal system, MRR 14.2 (95% CI 11.8-17.1)

Skin and subcutaneous tissue, MRR 4.4 (95% CI 3.0-6.5)

Infectious and parasitic agents, MRR 2.1 (95% CI 1.9-2.3)

Moreover, the RA patients lost almost twice as many potential years of life before age 75 per 10,000 patient-years, at 7,436, compared with only 4,083 among comparators. The highest percentages of years of life lost were for cancer, with 32%, and circulatory diseases, with 20%.

Standardized mortality ratios were high among young patients (ages 15 to 45) for the most common causes of death, at 5.40 (95% CI 3.56-7.86) for respiratory disease and 2.77 (95% CI 2.12-3.56) for circulatory disease, which reflects the low rates of death from these causes among the general population.

RA patients younger than 45 had an almost three-fold increased risk of death from cardiovascular causes. Previous research had suggested that traditional cardiovascular risk factors cannot fully account for this, and many researchers have suggested a role for chronic inflammation, the researchers noted.

The five-fold increased mortality risk from respiratory causes among patients younger than age 45 also was noteworthy: "Potential explanations of this excess risk include the pulmonary involvement in RA that weakens airway host defenses, making patients particularly susceptible to respiratory infections, and immunosuppressive treatment further elevates the risk."

Commenting to MedPage Today, Widdifield said: "Our detailed assessment of causes of death by age group offers new insights into the importance of cardiovascular and respiratory diseases as major contributors to early death in RA. Our findings highlight that more efforts are needed to reduce this inequality in survival for RA patients through co-morbid disease prevention strategies and management of co-morbid disease earlier in the disease course, such as better cardiovascular screening and increasing awareness among patients and care providers to be careful about infections."

A potential limitation of the analysis, the team said, was the lack of information about factors such as lifestyle and body mass index that could be confounding factors.

The study was supported by the Catherine and Fredrik Eaton Charitable Foundation and the Canadian Network for Advanced Interdisciplinary Methods, which is funded by the Canadian Institutes of Health Research Drug Safety & Effectiveness Network.

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